To date, there has been no information about the long-term replication mechanisms of the beta papillomaviruses. We have found that the beta HPV E2 proteins (HPV 5 and 8) associate with the peri-centromeric region of mitotic chromosomes and interact with the repeated ribosomal DNA genes found in this location. We have found that the domains of HPV8 E2 required for chromosomal association are also quite different from other papillomavirus E2 proteins, further supporting the finding that these proteins have different targets. We are developing marker viruses with selectable genes inserted into the viral genome to study the replication of this genus of viruses.